Jay D. Patel, Michael Briones, Mansi Mandhani, Shannon Jones, Divya Suthar, Rosemary Gray, Joelle Pettus, Courtney McCraken, Amanda Thomas, Christopher J. Petit
Emory University and Children’s Healthcare of Atlanta
United States
Journal of the American College of Cardiology
J Am Coll Cardiol 2021; 77: 2807-2818
DOI: 10.1016/j.jacc.2021.04.013
Abstract
Background: Anatomic interventions for pulmonary vein stenosis (PVS) in infants and children have been met with limited success. Sirolimus, a mammalian target of rapamycin inhibitor, has demonstrated promise as a primary medical therapy for PVS, but the impact on patient survival is unknown.
Objectives: The authors sought to investigate whether mTOR inhibition with sirolimus as a primary medical therapy would improve outcomes in high-risk infants and children with PVS.
Methods: In this single-center study, patients with severe PVS were considered for systemic sirolimus therapy (SST) following a strict protocol while receiving standardized surveillance and anatomic therapies. The SST cohort was compared with a contemporary control group. The primary endpoint for this study was survival. The primary safety endpoint was adverse events (AEs) related to SST.
Results: Between 2015 and 2020, our PVS program diagnosed and treated 67 patients with ≥moderate PVS. Of these, 15 patients were treated with sirolimus, whereas the remaining patients represent the control group. There was 100% survival in the SST group compared with 45% survival in the control group (log-rank p = 0.004). A sensitivity analysis was completed to address survival bias using median time from diagnosis of PVS to SST. A survival advantage persisted (log-rank p = 0.027). Two patients on sirolimus developed treatable AEs. Patients in the SST group underwent frequent transcatheter interventions with 3.7 catheterizations per person-year (25th to 75th percentile: 2.7 to 4.4 person-years). Median follow up time was 2.2 years (25th to 75th percentile: 1.2 to 2.9 years) in the SST group versus 0.9 years (25th to 75th percentile: 0.5 to 2.7 years) in the control group.
Conclusions: The authors found a survival benefit associated with SST in infants and children with moderate-to-severe PVS. This survival benefit persisted after adjusting the analysis for survival bias. There were 2 mild AEs associated with SST during the study period; both patients were able to resume therapy without recurrence.
Category
Medical Therapy. Efficacy or Lack of Efficacy
Medical Therapy. Adverse Effects or Lack of Adverse Effects
Segmental Pulmonary Venous Disease. Without a Focus on Pulmonary Hypertension
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes